Radiosynthesis of (±)-(2-((4-(2-[18F]fluoro-ethoxy)phenyl)bis(4-methoxy-phenyl)methoxy)ethylpiperidine-3-carboxylic acid: a potential GAT-3 PET ligand to study GABAergic neuro-transmission in vivo

✍ Scribed by Ralf Schirrmacher; Wilhelm Hamkens; Markus Piel; Ulrich Schmitt; Hartmut Lüddens; Christoph Hiemke; Frank Rösch

• Book ID: 102371363
• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 152 KB
• Volume: 44
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.492

✦ Synopsis

Abstract

A dysfunction of GABAergic neurotransmission is related to diseases such as epilepsy, Huntington‐disease and Parkinson‐syndrome. A new ^18^F‐fluorine labelled GABA transporter ligand for the GABA‐transporter subtype GAT‐3 was developed which may allow the in vivo visualisation of GABAergic neurotransmission. The precursors ethyl (2‐(4‐hydroxyphenyl)bis(4‐methoxyphenyl)‐methoxy)ethyl)‐piperidine‐3‐carboxylate and ethyl(2‐((4‐(2‐tosylethoxy)phenyl)‐bis(4‐methoxyphenyl)‐methoxy) ethyl)‐piperidine3‐carboxylate were synthesised and labelled by the use of 2‐[^18^F]fluoroethyltosylate or [^18^F]fluoride. Subsequent cleavage of the ester moiety gave the final product (±)‐(2‐((4‐(2‐[^18^F]fluoroethoxy)phenyl)bis(4‐methoxy‐phenyl)methoxy)ethyl)piperidine‐3‐carboxylic acid in a decay corrected yield of 33–36%. Preliminary biodistribution kinetics were determined with BALB/c mice ex vivo for brain, liver, kidney, spleen, blood and bone. (2‐((4‐(2‐[^18^F]fluoroethoxy)‐phenyl)bis(4‐methoxyphenyl)methoxy)‐ethyl) piperidine‐3‐carboxylic acid showed a maximum brain uptake after 1 h p.i. of about 0.3% ID/g. Copyright © 2001 John Wiley & Sons, Ltd.